Humoral immunity

humoral immunity, humoral immunity vs cell mediated immunityHumoral immunity or humoural immunity is the aspect of immunity that is mediated by macromolecules found in extracellular fluids such as secreted antibodies, complement proteins, and certain antimicrobial peptides Humoral immunity is so named because it involves substances found in the humors, or body fluids It contrasts with cell-mediated immunity Its aspects involving antibodies are often called antibody-mediated immunity

The study of the molecular and cellular components that form the immune system, including their function and interaction, is the central science of immunology The immune system is divided into a more primitive innate immune system, and acquired or adaptive immune system of vertebrates, each of which contains humoral and cellular components

Humoral immunity refers to antibody production and the accessory processes that accompany it, including: Th2 activation and cytokine production, germinal center formation and isotype switching, affinity maturation and memory cell generation It also refers to the effector functions of antibodies, which include pathogen and toxin neutralization, classical complement activation, and opsonin promotion of phagocytosis and pathogen elimination

Contents

1 History

2 Mechanism

21 B cell activation

22 B cell proliferation

23 Antibody-antigen reaction

3 Complement system

4 Antibodies

5 See also

6 References

7 Further reading

History

The concept of humoral immunity developed based on analysis of antibacterial activity of the serum components Hans Buchner is credited with the development of the humoral theory In 1890 he described alexins, or "protective substances", which exist in the blood serum and other bodily fluid and are capable of killing microorganisms Alexins, later redefined "complement" by Paul Ehrlich, were shown to be the soluble components of the innate response that lead to a combination of cellular and humoral immunity, and bridged the features of innate and acquired immunity

Following the 1888 discovery of the bacteria that cause diphtheria and tetanus, Emil von Behring and Kitasato Shibasaburō showed that disease need not be caused by microorganisms themselves They discovered that cell-free filtrates were sufficient to cause disease In 1890, filtrates of diphtheria, later named diphtheria toxins, were used to vaccinate animals in an attempt to demonstrate that immunized serum contained an antitoxin that could neutralize the activity of the toxin and could transfer immunity to non-immune animals In 1897, Paul Ehrlich showed that antibodies form against the plant toxins ricin and abrin, and proposed that these antibodies are responsible for immunity Ehrlich, with his friend Emil von Behring, went on to develop the diphtheria antitoxin, which became the first major success of modern immunotherapy The presence and specificity of compatibility antibodies became the major tool for standardizing the state of immunity and identifying the presence of previous infections

Major discoveries in the study of humoral immunity

Substance

Activity

Discovery

Alexins
Complement

Soluble components in the serum
that are capable of killing microorganisms

Buchner 1890,
Ehrlich 1892

Antitoxins

Substances in the serum that can neutralize
the activity of toxins, enabling passive immunization

von Behring and Kitasato 1890

Bacteriolysins

Serum substances that work with the
complement proteins to induce bacterial lysis

Mechanism ">edit]

In humoral immune response, first the B cells mature in the bone marrow and gain B-cell receptors BCR's which are displayed in large number on the cell surface

These membrane-bound protein complexes have antibodies which are specific for antigen detection Each B cell has a unique antibody that binds with an antigen The matured B cells migrate from bone marrow to lymph nodes or other lymphatic organs, where they begin to encounter pathogens

B cell activation

When a B cell encounters an antigen, it is bound to the receptor and taken inside by endocytosis The antigen is processed and presented on its surface again with MHC-II molecule

B cell proliferation

The B cell waits for the TH cell to bind to the complex This binding will activate TH cell and it releases cytokines that induce B cells to divide rapidly, making thousands of identical clones of B cell These daughter cells either become plasma cells or memory cells The memory B cells remain inactive here; later when these memory B cells encounter the same antigen due to reinfection, they divide and form Plasma cells On the other hand, the plasma cells produce a large number of antibodies which are released free in the circulatory system

Antibody-antigen reaction

Now these antibodies will encounter antigens and bind with them This will either interfere with the chemical interaction between host and foreign cells, or they may form bridges between their antigenic sites hindering their proper functioning, or their presence will attract macrophages or killer cells to phagocytose them

Complement system

Main article: Complement system

The complement system is a biochemical cascade of the innate immune system that helps clear pathogens from an organism It is derived from many small blood plasma proteins that work together to disrupt the target cell's plasma membrane leading to cytolysis of the cell The complement system consists of more than 35 soluble and cell-bound proteins, 12 of which are directly involved in the complement pathways The complement system is involved in the activities of both innate immunity and acquired immunity

Activation of this system leads to cytolysis, chemotaxis, opsonization, immune clearance, and inflammation, as well as the marking of pathogens for phagocytosis The proteins account for 5% of the serum globulin fraction Most of these proteins circulate as zymogens, which are inactive until proteolytic cleavage

Three biochemical pathways activate the complement system: the classical complement pathway, the alternate complement pathway, and the mannose-binding lectin pathway The classical complement pathway typically requires antibodies for activation and is a specific immune response, while the alternate pathway can be activated without the presence of antibodies and is considered a non-specific immune response Antibodies, in particular the IgG1 class, can also "fix" complement

B cell activation is a large part of the humoral immune response

Antibodies

Main article: Antibody

Immunoglobulins are glycoproteins in the immunoglobulin superfamily that function as antibodies The terms antibody and immunoglobulin are often used interchangeably They are found in the blood and tissue fluids, as well as many secretions In structure, they are large Y-shaped globular proteins In mammals there are five types of antibody: IgA, IgD, IgE, IgG, and IgM Each immunoglobulin class differs in its biological properties and has evolved to deal with different antigens Antibodies are synthesized and secreted by plasma cells that are derived from the B cells of the immune system

An antibody is used by the acquired immune system to identify and neutralize foreign objects like bacteria and viruses Each antibody recognizes a specific antigen unique to its target By binding their specific antigens, antibodies can cause agglutination and precipitation of antibody-antigen products, prime for phagocytosis by macrophages and other cells, block viral receptors, and stimulate other immune responses, such as the complement pathway

An incompatible blood transfusion causes a transfusion reaction, which is mediated by the humoral immune response This type of reaction, called an acute hemolytic reaction, results in the rapid destruction hemolysis of the donor red blood cells by host antibodies The cause is usually a clerical error, such as the wrong unit of blood being given to the wrong patient The symptoms are fever and chills, sometimes with back pain and pink or red urine hemoglobinuria The major complication is that hemoglobin released by the destruction of red blood cells can cause acute renal failure

^ Mentioned in On the Formation of Specific Anti-Bodies in the Blood, Following Upon Treatment with the Sera of Different Animals, George H F Nuttall American Naturalist, Vol 35, No 419 Nov, 1901, pp 927-932

Further reading

The following article reviews some of the early experiments that laid the foundations of the humoral theory: Orji Theddeus C, S J and Charles Norris 1897 The Bactericidal Action of Lymph Taken From the Thoracic Duct of the Dog Full Text-pdf Journal of Experimental Medicine Vol 2, Issue 6, 701-709

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